This application is being submitted to PA-18-591 in accordance with NOT-OD-18-194. The proposed supplement INCLUDE project is entitled: ?Upper Airway Structure and Function and Risk for OSA in Children with Down Syndrome?. The project is within the scope of R01 HL130468 entitled: ?A Computational Biomechanical Airway Model for Obese Children at Risk for OSAS? that focuses on implementing state-of-the-art magnetic resonance imaging (MRI) during wake and sleep conditions (Aim 1A) using analytical and machine learning techniques to determine the static (3D) and dynamic (4D) architecture and tissue characteristics of the upper airway in wake and sleep conditions (Aim 1B). These methods are coupled with computational fluid dynamics (CFD) (Aim 2A) and biomechanical modeling (Aim 2B) to establish the biomechanical basis of OSAS in children with obesity. The parent grant also evaluates the impact of treatment such as adenotonsillectomy or continuous positive airway pressure (CPAP) on airway mechanics (Aim 3A) and the clinical utility of image-based airway mechanical parameters in OSAS (Aim 3B). The tools and methodologies used in the parent project will be integrated in all Aims of this INCLUDE project. The proposed project addresses 2 important IC-specific priorities of NHLBI: 1) ?Incorporation of individuals with Down syndrome into existing disease cohorts and clinical trials directed toward sleep apnea. This could include collection of tissue or blood specimens and -omics data generation and analysis, imaging, and computational modeling?, 2) Identification of potential risk and resilience factors that make individuals with Down syndrome susceptible to transient or persistent blood disorders and congenital heart disease?. The problem: Down syndrome (DS) (trisomy 21) is the most common genetic cause of developmental disability and mental retardation with an incidence of 1/800 live births (1). The prevalence of OSA in these children is very high and estimated between 50-95% (2-5), and much higher than the 1-4% prevalence in the general pediatric population (6). OSA has detrimental consequences in children, including cardiovascular, metabolic, and cognitive effects (6). This is particularly true for children with Down syndrome who are already predisposed to congenital heart anomalies and developmental delay. Therefore, the American Academy of pediatrics (AAP) emphasizes the need to screen for OSA within the first 6 months of life in all children with Down syndrome and continue to evaluate for the disorder on all medical encounters thereafter throughout childhood (7). Anatomical factors related to the Down syndrome phenotype have been attributed to the causation of OSA in this group. These include midfacial and mandibular hypoplasia (8-11), enlarged tongue (12, 13), adenoid and tonsilar hypertrophy (13, 14), laryngo-tracheal anomalies (15), and obesity (16-19). In addition, reduced neuromuscular tone has been suspected of having a role in the development of OSA in these subjects (3). Traditional methods to evaluate the upper airway in children with DS include plain lateral neck radiograph, cephalometric measurements, airway fluoroscopy, and nasal pharyngoscopy (8, 15, 20, 21). However, these methods provide only limited information regarding the entire upper airway structure. During the years our group has developed,applied, and published seminal work on the upper airway structure and function of children using MRI methodology (22-35). This body of work on normal children and children with craniofacial abnormalities including DS created a large MRI database that is the basis for the current proposal.